1,2,4-Triazole/oxime hybrids as new strategy for nitric oxide donors: Synthesis, anti-inflammatory, ulceroginicity and antiproliferative activities

Eur J Med Chem. 2014 Jan:71:185-98. doi: 10.1016/j.ejmech.2013.11.006. Epub 2013 Nov 12.

Abstract

A series of novel nitric oxide (NO) donating triazole/oxime hybrids was prepared and evaluated for their anti-inflammatory activity and antiproliferative activity. Most of the tested compounds showed significant anti-inflammatory activity using carrageenan-induced rat paw edema method compared to indomethacin. Calculation of the ulcer indices and histopathological investigation indicated that the prepared NO-donating oximes exhibited less ulcerogenicity compared to their ketone intermediates and indomethacin. The NO-donating oximes 7i and 7k achieved remarkable cell growth inhibition activity against most of the tested cell lines. Compound 7k was found to be with high selectivity against CNS subpanel with selectivity ratio of 11.99 at GI₅₀ level.

Keywords: 1,2,4-Triazole; Anti-inflammatory; Antiproliferative; Nitric oxide donors; Ulcerogenicity.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Edema / drug therapy
  • Humans
  • Male
  • Neoplasms / drug therapy
  • Nitric Oxide Donors / adverse effects
  • Nitric Oxide Donors / chemistry
  • Nitric Oxide Donors / pharmacology*
  • Oximes / adverse effects
  • Oximes / chemistry
  • Oximes / pharmacology*
  • Rats
  • Stomach Ulcer / chemically induced
  • Triazoles / adverse effects
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Nitric Oxide Donors
  • Oximes
  • Triazoles
  • 1,2,4-triazole